Methods for integrating a functional component into a microfluidic device

ABSTRACT

Injection molding is used to form microfluidic devices with integrated functional components. One or more functional components are placed in a mold cavity, which is then closed. Molten thermoplastic resin is injected into the mold and then cooled, thereby forming a solid substrate including the functional component(s). The solid substrate including the functional component(s) is then bonded to a second substrate, which may include microchannels or other features.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of prior U.S. patentapplication Ser. No. 10/754,286 originally filed Jan. 8, 2004 entitled,“Microfluidic Structures and Methods for integrating a FunctionalComponent into a Microfluidic Device,” and issued as U.S. Pat. No.7,351,380 on Apr. 1, 2008. This application and patent are incorporatedby reference in their entirety and for any purpose.

STATEMENT OF GOVERNMENT INTEREST

This invention was made with Government support under governmentcontract no. DE-AC04-94AL85000 awarded by the U.S. Department of Energyto Sandia Corporation. The Government has certain rights in theinvention, including a paid-up license and the right, in limitedcircumstances, to require the owner of any patent issuing in thisinvention to license others on reasonable terms.

TECHNICAL FIELD

The present invention relates to microfluidic devices, and moreparticularly, to integrating functional components into microfluidicdevices.

BACKGROUND OF THE INVENTION

Microfluidic devices are increasingly used to manipulate and handlesmall fluid volumes for reactive, analytical, sensing and otherapplications. Although microfluidic devices contain features on themicroscale-such as channels and chambers-the devices frequently mustinteract with other external devices or assemblies. For example,microfluidic devices may require connection to a larger fluid source orintegration with a sensor, pumping or other external assembly.

One approach to this integration involves securing discrete, functionalcomponents, such as flow connectors, to a microfluidic device using anadhesive. However, adhering each component in this manner may limit thepressure that can be applied before leakage occurs between the componentand the device substrate. Alignment errors may also be introduced aseach component is independently adhered to the device substrate.Further, this technique limits the components that may be attached tothe device to those that are chemically compatible with the adhesiveused to attach them.

There is therefore a need to improve the technology used to formconnections between a microfluidic device and an external component, aswell as to increase the range of functional components that can beconnected to a microfluidic device.

There is also a desire to provide a method for rapidly formingmicrofluidic replicates in a manner that incorporates the neededfunctional components during the replication process.

SUMMARY OF THE INVENTION

In accordance with a first aspect of the invention, a method forintegrating a functional component to a microfluidic device is provided.A functional component is placed into a predetermined location in a moldcavity. Resin is injected into the mold cavity and cooled, therebyforming a solid substrate containing the functional component, which isbonded to a second substrate to form the functional microfluidic device.The second substrate, in some embodiments, contains at least onemicrofluidic channel.

In accordance with a second aspect of the invention, a microfluidicdevice is provided: A functional component is embedded in a solidsubstrate in a predetermined location. A second substrate is bonded tothe solid substrate such that the functional component impartselectrical, optical, mechanical, or other functionality to the device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is an isometric view depicting a flow connector for integrationwith a microfluidic device according to an example of the invention.

FIG. 1B is a cross-sectional view of the flow connector according to anexample of the invention.

FIGS. 2A-2E are cross-sectional views depicting one embodiment of amicrofluidic device according to the present invention at various stagesas the device is being made.

FIG. 3 is a flow chart of a method of forming a microfluidic devicehaving an integrated functional component, according to an example ofthe invention.

FIG. 4 is a schematic of a microfluidic device according to an exampleof the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Embodiments of the present invention provide methods for integrating afunctional component into a microfluidic device. A functional component,as used herein, refers generally to any component of interest that maybe advantageously integrated with a second substrate to form afunctional device, as described further below. In some embodiments, thefunctional component provides electrical, mechanical, optical, or otherfunctionality to a microfluidic device. Accordingly, functionalcomponents include flow connectors, circuits or other electronic chipsor devices, optical waveguides, fiber optic cables, lenses, RFtransmitters or receivers, flow detectors, flow regulators, othersensors or transducers, laser diodes, light emitting diodes, pressuretransducers, optical filters optical elements, reservoirs, electrodes,salt-bridges, membranes, flow valves, high voltage power supplies, andthe like. Such functional components may be fabricated from a wide rangeof polymeric, metal or ceramic materials. Substantially any componentsuitable to withstand the injection molding process described below maybe used as a functional component as described herein.

Functional components useful in embodiments of the present inventioninclude, for example, polymer fittings and flow connectors describedfurther in U.S. patent application Ser. No. 10/405,842, filed 2 Apr.2003, entitled “Micromanifold Assembly”, and U.S. patent applicationSer. No. 10/405,204, filed 2 Apr. 2003 entitled “High Pressure CapillaryConnector,” all of which are hereby incorporated by reference in theirentirety.

FIG. 1A depicts a flow connector 10 that may be integrated into amicrofluidic device in accordance with an embodiment of the presentinvention. FIG. 1B depicts a cross-sectional view of the flow connector10. As shown in FIGS. 1A and 1B, the flow connector 10 includes a flange25 and an annular groove 20 that advantageously increase the couplingbetween the connector 10 and an injected resin. The flow connector 10further has a square body portion 30 to reduce any rotation of theconnector 10 within a solid substrate (not shown in FIGS. 1A, 1B) afterthe molding process is complete. Although a flow connector 10 isillustrated in the exemplary FIGS. 1A and 1B, other functionalcomponents may be used in other embodiments and may include a groove orother structure to strengthen the coupling between the component and theresin and may also include a square or other profile to reduce rotation.The flow connector shown in FIGS. 1A and 1B is approximately 0.2″ inheight and 0.2″ in width. Different dimensions, however, may be used inother embodiments.

FIG. 2A shows an empty mold cavity 55. As shown in FIG. 2B, functionalcomponents labeled 50 are placed into the mold cavity 55. Although fourfunctional components 50 are shown in FIG. 2A, it is to be understoodthat any number of functional components may be used including 1, 2, 3,4, 5, 6, 7, 8, 9, and 10 functional components. Morefunctional-components are used in other embodiments. Further, acombination of different functional components 50 may be placed into themold cavity in some embodiments. The mold cavity 55 is defined by a moldbase suitable for injection molding, as is known in the art. Such moldbases typically are made from tool steel and comprise a top 70 andbottom 65, which are mounted on facing platens of an injection moldingmachine. Upon closure of the platens, the mold cavity 55 is formed bythe bottom 65 and top 70 of the mold base.

Injection molding machines may be vertically-clamping orhorizontally-clamping, as is known in the art, and either may be used.Vertically-clamping machines are advantageous in embodiments of thepresent invention. In some embodiments, horizontally-clamping machinesrequire use of other fixtures to prevent the functional components fromfalling out of the mold. In some embodiments, the mold base defining thecavity 55 has more than two pieces (the top 65 and the top 70, as shownin FIG. 2). Generally, any equipment suitable for injection molding maybe used.

The mold cavity 55 may be of substantially any size or shape suitablefor the molding process, and may include tooling to introduce moldedfeatures such as microfluidic channels or chambers. The mold cavity mayalso include depressions 90 or protrusions, which can be used toposition and fixture the functional components 50 that are placed withinthe mold cavity prior to resin injection as shown in FIGS. 2A and 2B.The depressions or protrusions are positioned to hold the functionalcomponents 50 in place in a predetermined location, such that whenbonded with a second substrate 85, functionality is added to theresultant device. Depending on the functional components 50 used, thefunctionality added may be electrical, optical, mechanical, or otherfunctionality. Such cavity features may be contained in either the top70 or the bottom 65 of the mold base. Upon sealing of the mold cavity55, the inserted functional components 50 are sealed or pressed againstthe opposing surfaces of the mold cavity 55. This provides fixturing ofthe components and also seals any channels within components such asfluidic connectors from being filled by injected resin. For example, inthe embodiment shown in FIG. 2B, flow connectors shown in FIGS. 1A and1B are present in the sealed mold 55 cavity. The lip of the flowconnectors is pressed against the top 70 while the other end of theconnectors is pressed into a depression 90 in another surface of thecavity 55 thus limiting or preventing resin from filling a channelwithin the flow connector. In some embodiments, a compliant shim orgasket (not shown) may be placed between the functional component 50 andthe mold cavity 55 to prevent damage to the flow connector and/or toenhance the seal between the functional component and the mold.

While the mold cavity depressions 90 and protrusions described above maybe machined directly into the mold base 65 forming the mold cavity 55,in some embodiments, a cavity tool 60 which provide the requireddepressions, protrusions or other features which allow positioning andfixturing of the added functional components is placed in the moldcavity 55. Such cavity tools may also contain microfluidic features suchas channels and chambers. In some embodiments, the cavity tool 60 isremovable. In some embodiments, the cavity tool 60 is removable, suchthat the mold base may be used without the cavity tool 60, or anothercavity tool placed in the mold base. The cavity tool 60 may generally bemade of any material suitable to withstand the injection molding processincluding for example metals such as steel.

Injection molding proceeds, as is known in the art and shown in FIG. 2C,by injecting resin 75 into the mold cavity 55. Any resin suitable forinjection molding may be used. Typical thermoplastic resins includeacrylics, polyolefins, polycarbonates, polyesters and many others. Insome embodiments, thermosets are used. Of interest in many microfluidicapplications are optically transparent resins including cyclic-olefincopolymers such as ethylene-norbornene copolymers and dicyclopentadienecopolymers and others. The particular resin chosen will depend on theapplication, the materials of the functional components used, and thematerial of the second substrate 85 to which the substrate containingthe functional components will be bonded. In some embodiments, thefunctional components used are formed from one or more polymericmaterials having a glass transition or melting point temperature higherthan the glass transition temperature of the polymer resin used to formthe substrate in the injection molding process. However, in otherembodiments the functional component may not have a glass transitiontemperature higher than that of the resin and the difference in thermalproperties between a functional component and the resin may beadvantageously used to increase the strength of the interaction betweenthe resin and the component. In some embodiments, the functionalcomponent is made from or coated with the same resin used in theinjection molding process. Accordingly, as is known in the art, duringinjection molding, molten resin is injected into a mold, and as itcools, forms a solid substrate.

In a preferred embodiment, a commercially available vertical injectionmolding machine was used such as the TH60-VSE from Nissei America, Inc.Anaheim, Calif. A custom mold base was designed and fabricated, whichallowed cavity tool inserts to be placed in either side of the mold base65. The use of cavity tool inserts also allows adjustments in the depthof the cavity 55.

As shown in FIGS. 2C and 2D, the resin 75 in the mold cavity 55 forms asolid substrate 80 including the functional components 50. The solidsubstrate 80 is then removed from the mold cavity 55. As shown in FIG.2E, the solid substrate 80 including the functional components 50 isbonded to a second substrate 85. The bonding occurs through any of avariety of methods known in the art, including fusion bonding,adhesives, and the like.

The second substrate 85 may be made of any of a variety of materialsaccording to embodiments of the present invention, including, forexample, polymers such as thermoplastics or elastomers, metals such assteel, titanium, gold, aluminum, semiconductors such as silicon or GaAs,and insulators such as glass, quartz, silicon dioxide, and the like. Theparticular substrate 85 selected will depend on the application, thefeatures in the substrate 85, the resin used in the injection moldingprocess, and the functional components contemplated. The secondsubstrate 85 to which the injection molded substrates are bonded mayhave a variety of features, in accordance with embodiments of theinvention, including, for example one or more mixers, pumps, valves,heaters, coolers, channels, chambers, fluid ports, and the like.

By way of summary, a method of forming an integrated microfluidic deviceaccording to an embodiment of the present invention is shown in FIG. 3.A mold base defining at least one cavity is provided (see step 100). Aninterchangeable cavity tool may be placed in a mold base, or the moldcavity tooling may be an integral part of the mold base, in accordancewith embodiments of the present invention. At least one functionalcomponent is placed in the mold cavity and/or into a depression definedby the mold base (step 110). Resin is injected into the mold cavity(step 120). The resin is cooled, thereby forming a solid substrateincluding the functional component (step 130), which can be removed fromthe mold cavity. The solid substrate including the functional componentis then bonded to a second substrate (step 140). In some embodiments,further components may be connected to the bonded device. For example,in one embodiment the flow connector 10 is incorporated into aninjection molded solid substrate, and bonded to a second substratehaving a microchannel, such that access to the microchannel is providedthrough the flow connector 10. Accordingly, tubing and an external pumpmay be attached to one or more of the flow connectors, in accordancewith an embodiment of the invention. For example, in a preferredembodiment the flow connector is attached to a silica capillary tube bya compression fitting that is attached by screws (not shown) to the flowconnector.

A top-down view of a device according to an embodiment of the presentinvention is shown schematically in FIG. 4. A microchannel 200 isprovided in a microfluidic substrate having an inlet and outlet. Asecond microchannel 210 is also provided in the microfluidic substrate,with a second inlet and outlet. A cavity tool is machined to hold flowconnectors in positions complementary to the inlets and outlets of themicrochannels 200 and 210. The flow connectors incorporated into aninjection molded substrate, as described above, and bonded to thesubstrate containing the microchannels 200 and 210 such that the flowconnectors 220 are aligned with the microchannel inlets and outlets.Accordingly, as shown in FIG. 4, fluid enters and exits either themicrochannel 200 or the microchannel 210 through the flow connectors220. In a similar manner, other types of functional components may bealigned to features, such as electrodes, optically transparent regions,thermally conductive regions, and the like, of a second substrate.

After the injection molded substrate has been formed, it is bonded witha second substrate. In some embodiments, the bond forms a watertightseal and will allow for the successful operation of a microfluidicdevice. The bonding process typically involves an alignment step, insome embodiments of the two substrates one with the flow connectors theother containing the channel, to allow access to the microfluidicfeatures. In some embodiments, no alignment is necessary. After properlyaligned, if necessary, the two substrates are bonded together to producea functioning microfluidic device. The bonding process may include hotdie bonding, thermal diffusion bonding, solvent bonding, infraredwelding, ultraviolet irradiation, ultrasonic welding, or other joiningtechnologies known in the art, or combinations thereof. In someembodiments, an adhesive, seal, or gasket, is placed between the twosubstrates.

Embodiments of devices according to the present invention are able tooperate at increased pressures relative to those having functionalcomponents adhesively bonded with epoxies or other adhesive materials tothe surface. For example, in the embodiment shown schematically in FIG.4, fluid can be pumped through the channel 210 or the channel 200 at apressure typically in the range of 100-970 psi. In other embodiments, alower pressure is used. A similar device utilizing a flow connectoradhesively bonded to the surface withstood only a pressure of about 680psi.

From the foregoing it will be appreciated that, although specificembodiments of the invention have been described herein for purposes ofillustration, various modifications may be made without deviating fromthe spirit and scope of the invention. Accordingly, the invention is notlimited except as by the appended claims.

What is claimed is:
 1. A method for integrating a functional component to a microfluidic device, the method comprising: embedding the functional component in a solid substrate, including: placing the functional component into a mold cavity; injecting resin into the mold cavity; and cooling the injected resin, thereby forming a solid substrate containing the functional component; and bonding the solid substrate comprising the functional component to a second substrate, wherein said bonding the solid substrate includes aligning an opening of the functional component to a fluid port of a fluid channel in the second substrate.
 2. A method according to claim 1, wherein the act of placing comprises placing the functional component into a predetermined position in the mold cavity.
 3. A method according to claim 1, wherein the second substrate forms at least a portion of a microfluidic device.
 4. A method according to claim 1, further comprising placing a plurality of functional components into the mold, and wherein the solid substrate formed contains the plurality of functional components.
 5. A method according to claim 1 wherein the act of placing the functional component into a mold cavity comprises: providing a mold base defining a cavity having a predetermined shape to hold the functional components in a predetermined location; and placing the functional component into the cavity.
 6. A method according to claim 5 wherein the cavity dimensions and the mold base comprises a mold insert.
 7. A method according to claim 1 wherein the second substrate comprises a plurality of fluid channels.
 8. A method according to claim 1 wherein the second substrate comprises a substrate chosen from the group of substrates consisting of glass, polymer, silicon, thermosets, thermoplastic, and combinations thereof.
 9. A method according to claim 1, wherein the functional component is selected from the group of functional components consisting of a flow connector, a circuit, an optical waveguide, an electrical interconnect, a fiber optic cable, a lens, a radio-frequency transmitter, a flow detector, a flow regulator, a laser diode, a light emitting diode, a pressure transducer, an optical filter or optical element, a reservoir, an electrode, a salt-bridge, a membrane, a flow valve, a high voltage power supply and combinations thereof.
 10. A method according to claim 1, wherein the functional component comprises a flow connector.
 11. A method according to claim 1, wherein the complementary feature comprises an electrical interconnect.
 12. A method according to claim 1 wherein the act of bonding the solid substrate to the second substrate comprises using a joining process selected from the group of joining processes consisting of hot die bonding, thermal diffusion bonding, solvent bonding, infrared welding, ultraviolet irradiation, ultrasonic welding, and combinations thereof.
 13. A method according to claim 1 wherein the act of bonding the solid substrate to the second substrate comprises applying an adhesive between at least a portion of the solid substrate and the second substrate.
 14. A method according to claim 1 wherein the act of bonding the solid substrate to the second substrate comprises placing a seal between the solid substrate and the second substrate.
 15. A method according to claim 1, wherein said functional component is formed prior to injecting the resin into the mold cavity.
 16. A method according to claim 1, wherein said injecting the resin into the mold cavity comprises surrounding the functional component in the mold cavity with the injected resin. 